Abstract

The cardiac conduction system (CCS) consists of the sinus node (pacemaker of the heart responsible for the initiation of the cardiac action potential), atrioventricular node (in essence a relay station for the action potential from the atria to the ventricles) and the His-Purkinje system (system of fibres responsible for the transmission of the action potential throughout the ventricles). The CCS is responsible for the initiation and coordination of the heart beat. Dysfunction or disease of the CCS causes a wide range of arrhythmias including all bradyarrhythmias (sinus bradycardia, heart block and bundle branch block) and many tachyarrhythmias (many focal atrial tachycardias, atrioventricular nodal reentrant tachycardia, arguably ventricular outflow tract ventricular tachycardia and bundle branch reentry). The CCS is also arguably involved in Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). The Purkinje fibres are prone to early and late afterdepolarizations. The list of arrhythmias involving the CCS is extensive! Our work and the work of others shows that the CCS becomes dysfunctional or diseased in a wide variety of heart conditions – in heart failure, following a myocardial infarction, in pulmonary hypertension, possibly in diabetes, possibly in obesity and even in veteran athletes. For example, the Danish CARISMA study has shown that bradyarrhythmias account for half of deaths of myocardial infarction patients. Our work suggests that the CCS is much more sensitive to insults than the working myocardium of the heart. The impression is that, if a part of the heart is to fail, it is likely to be the CCS . The CCS is the Achilles’ heel of the heart. In my talk, I will explore this thesis by discussing our work on heart failure, myocardial infarction, pulmonary hypertension, athletes and warming sea temperatures and fish. I will also discuss the implications of an intrinsic circadian rhythm in the CCS . Finally, I will describe our current experiments which suggest that we can prevent CCS dysfunction in heart failure and athletes by targeting certain micro-RNAs.